Effects of nucleic acid local structure and magnesium ions on minus-strand transfer mediated by the nucleic acid chaperone activity of HIV-1 nucleocapsid protein

HIV-1 nucleocapsid protein (NC) is a nucleic acid chaperone, which is required for highly specific and efficient reverse transcription. Here, we demonstrate that local structure of acceptor RNA at a potential nucleation site, rather than overall thermodynamic stability, is a critical determinant for the minus-strand transfer step (annealing of acceptor RNA to (−) strong-stop DNA followed by reverse transcriptase (RT)-catalyzed DNA extension). In our system, destabilization of a stem-loop structure at the 5′ end of the transactivation response element (TAR) in a 70-nt RNA acceptor (RNA 70) appears to be the major nucleation pathway. Using a mutational approach, we show that when the acceptor has a weak local structure, NC has little or no effect. In this case, the efficiencies of both annealing and strand transfer reactions are similar. However, when NC is required to destabilize local structure in acceptor RNA, the efficiency of annealing is significantly higher than that of strand transfer. Consistent with this result, we find that Mg2+ (required for RT activity) inhibits NC-catalyzed annealing. This suggests that Mg2+ competes with NC for binding to the nucleic acid substrates. Collectively, our findings provide new insights into the mechanism of NC-dependent and -independent minus-strand transfer

Atomically Trading with Roger: Gambling on the success of a hardfork

We present atomic trade protocols for Bitcoin and Ethereum that can bind two parties to swap coins in the event that two blockchains emerge from a single “pre-fork” blockchain. This work is motivated by a bet between two members of the Bitcoin community, Loaded and Roger Ver, to trade 60,000 bitcoins in the event that Bitcoin Unlimited’s planned hardfork occurs and the blockchain splits into two distinct forks. Additionally we study several ways to provide replay protection in the event of hardfork alongside a novel mechanism called migration inputs. We provide a detailed survey and history of previous softforks and hardforks in Ethereum and Bitcoin

Impressing for Success: A Gendered Analysis of a Key Social Capital Accumulation Strategy

Social capital theory assesses the career benefits that accrue to individuals from the stock of relationships they have. Such benefits can be in the form of guidance and advice, access to key projects and assignments and help with setting up business deals. However, when assessing whether such career-enhancing resources are available equally to men and women, we find that gender impacts on the access to and accumulation of social capital. The article seeks to address two key research questions. The first is whether women are aware of the need to accumulate social capital to advance their careers and the second is whether they use impression management techniques in order to assist them in doing this. Findings are reported from a study in an international consulting firm with 19 female consultants. In respect of research question one the findings indicate that women in the sample are aware of the need to accumulate social capital to advance their careers; with particular emphasis being placed on the importance of gaining access to influential sponsors. In respect of research question two, the findings confirm that women in the sample do perceive the necessity to utilise impression management techniques to help them to accumulate social capital. This is done in a defensive way and is linked to ensuring that one is seen as ambitious, likable and available. It is argued that these are key organizational norms, and it is perceived that in order to accumulate social capital, women need to actively work to dispel the negative stereotypes that attach to them because of their gender. The article calls for greater recognition of the impact that masculine organizational cultures have on the career development of women, who not only have to perform at a high level but are also required to expend additional energy conforming to masculine organizational cultures they have had little say in creating

Abnormalities of saccadic eye movements in dementia due to Alzheimer's disease and mild cognitive impairment

Background: There is increasing evidence that people in the early stages of Alzheimer's disease (AD) have subtle impairments in cognitive inhibition that can be detected by using relatively simple eye-tracking paradigms, but these subtle impairments are often missed by traditional cognitive assessments. People with mild cognitive impairment (MCI) are at an increased likelihood of dementia due to AD. No study has yet investigated and contrasted the MCI subtypes in relation to eye movement performance. Methods: In this work we explore whether eye-tracking impairments can distinguish between patients with the amnesic and the non-amnesic variants of MCI. Participants were 68 people with dementia due to AD, 42 had a diagnosis of aMCI, and 47 had a diagnosis of naMCI, and 92 age-matched cognitively healthy controls. Results: The findings revealed that eye-tracking can distinguish between the two forms of MCI. Conclusions: The work provides further support for eye-tracking as a useful diagnostic biomarker in the assessment of dementia

Neuropsychiatry of creativity.

In this paper, we review in brief the development of ideas that over time have tried to explain why some individuals are more creative than others and what may be the neurobiological links underlying artistic creativity. We note associations with another unique human idea, that of genius. In particular, we discuss frontotemporal dementia and bipolar, cyclothymic mood disorder as clinical conditions that are helping to unravel the underlying neuroanatomy and neurochemistry of human creativity. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity"

Does the stock market gender stereotype corporate boards? Evidence from the market's reaction to directors' trades

Pre-print version. The definitive version is available at http://onlinelibrary.wiley.com/Attitudes towards male and female managers within organizations are well documented, but how the stock market perceives their relative capabilities is less studied. Recent evidence documents a negative short-run market reaction to the appointment of female chief executive officers and suggests that female executives are less informed than their male counterparts about future corporate performance. These results appear to dispute the stock market value of having women on corporate boards. However, such short-run market reactions may retain a ‘gender bias’, reflecting the prevalence of negative stereotypes, where the market reacts to ‘beliefs’ rather than ‘performance’. This study tests for such bias by examining the stock market reaction to directors' trades in their own companies' shares, by measuring both the short-run and longer-term returns after the directors' trades. Allowing for firm and trade effects, some evidence is found that, in the longer term, markets recognize that female executives' trades are informative about future corporate performance, although initially markets underestimate these effects. This has important implications for research that has attempted to assess the value of board diversity by examining only short-run stock market responses

Electrostatic free energy landscapes for nucleic acid helix assembly

Metal ions are crucial for nucleic acid folding. From the free energy landscapes, we investigate the detailed mechanism for ion-induced collapse for a paradigm system: loop-tethered short DNA helices. We find that Na(+) and Mg(2+) play distinctive roles in helix–helix assembly. High [Na(+)] (>0.3 M) causes a reduced helix–helix electrostatic repulsion and a subsequent disordered packing of helices. In contrast, Mg(2+) of concentration >1 mM is predicted to induce helix–helix attraction and results in a more compact and ordered helix–helix packing. Mg(2+) is much more efficient in causing nucleic acid compaction. In addition, the free energy landscape shows that the tethering loops between the helices also play a significant role. A flexible loop, such as a neutral loop or a polynucleotide loop in high salt concentration, enhances the close approach of the helices in order to gain the loop entropy. On the other hand, a rigid loop, such as a polynucleotide loop in low salt concentration, tends to de-compact the helices. Therefore, a polynucleotide loop significantly enhances the sharpness of the ion-induced compaction transition. Moreover, we find that a larger number of helices in the system or a smaller radius of the divalent ions can cause a more abrupt compaction transition and a more compact state at high ion concentration, and the ion size effect becomes more pronounced as the number of helices is increased